Oncosis-inducing cyclometalated iridium(<scp>iii</scp>) complexes

Guan, Ruilin; Chen, Yu; Zeng, Leli; Rees, Thomas W.; Jin, Chengzhi; Huang, Juanjuan; Chen, Zhe‐Sheng; Ji, Liang‐Nian; Chao, Hui

doi:10.1039/c8sc01142g

Cited by 115 publications

(101 citation statements)

References 80 publications

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“…It was confirmed that ATP insufficient was one of the reason in oncosis. 11,17) At the same time, the result of DMF in our study had fully verified the common phenotype of oncosis. In the process of apoptosis, some chemotherapeutic agents cause ATP decrease, ROS accumulation, Ca 2+ elevation and MMP loss.…”

Section: Dmf Exert Potent Effect In Suppressing Proliferation Againstsupporting

confidence: 76%

“…As documented that the ATP level plays an important role in cell death, which determine how the cell dies. 11,17) Mitochondrial dysfunction is one of the important features of programmed cell death (PCD). The loss of MMP and the opening of membrane permeability transition pore (PTP) related to cell death closely.…”

Section: Dmf Exert Potent Effect In Suppressing Proliferation Againstmentioning

confidence: 99%

“…10) As so far, the majority of literatures use apoptosis ways to study oncosis, including some signal cascades that similar to the mechanism of apoptosis (but there are still some differences). 11,12) Therefore, we used some similar ways of apoptosis to research the difference between 5-Fu and DMF in mechanisms. The study suggested that the mechanism of apoptosis induced by 5-Fu were mainly involved in caspase family of extracellular and intracellular pathway, such as caspases-3, -8, and -9.…”

Section: Introductionmentioning

confidence: 99%

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The Cell Death Phenotype of MGC-803 Cells Inducing with “Dextran-Magnetic Layered Double Hydroxide-Fluorouracil” Drug Delivery System and Fluorouracil

Pei

Wang

Shu

et al. 2019

Biological & Pharmaceutical Bulletin

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The purpose of the paper is to study the differences in cell death mechanism of MGC-803 induced by "dextran-magnetic layered double hydroxide-fluorouracil" (DMF) drug delivery system and 5-Fluorouracil (5-Fu), respectively. The inhibitory effect on the proliferation was detected via CCK-8. The morphology of cell death was detected by transmission electron microscopy (TEM). Intracellular ATP, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and Cytosolic Free Ca (Ca 2) level were detected via some methods. The result showed that DMF had more obvious effect in suppressing proliferation compared with 5-Fu, and changed cell death pattern of 5-Fu from apoptosis to oncosis. The ATP decrease, MMP loss, Ca 2 increase, the activation of uncoupling protein-2 (UCP-2) and calpain-1 were significant after DMF exposure. However, DMF did not result in ROS accumulation. DMF could involve in activation of porimin, and the cascade reaction of caspases-3,-7,-9, and-12 and poly ADP-ribose polymerase (PARP) through Western blot. DMF showed a stronger injury on nuclear membrane in the cascade reaction of caspases-6,-8 and lamin-A. DMF triggered rapid depletion of ATP, which was consistent with the phenotype of oncosis. Endogenous mitochondrial apoptosis might not be the main cause of cell swelling. DMF could induce strong endoplasmic reticulum stress (ERS) effect, there might be some signaling pathways related with ERS during the process of oncosis. The calpain system might not be a key factor for structural damage in oncosis induced by DMF. DMF could induce the caspases cascade reactions similar to apoptosis, but inflicted a more strong damage on nuclear membrane and PARP.

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Section: Dmf Exert Potent Effect In Suppressing Proliferation Againstsupporting

confidence: 76%

Section: Dmf Exert Potent Effect In Suppressing Proliferation Againstmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Cell Death Phenotype of MGC-803 Cells Inducing with “Dextran-Magnetic Layered Double Hydroxide-Fluorouracil” Drug Delivery System and Fluorouracil

Pei

Wang

Shu

et al. 2019

Biological & Pharmaceutical Bulletin

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“…Thus, we further investigated whether complexes induce apoptosis through the mitochondrial damage by measuring the MMP changes . The MMP loss and the ROS overload are the main pathways in the mitochondria to carry out cell death , . We investigated the intracellular MMP loss and ROS production in Ru2 ‐treated A549 cells by using fluorescent probe JC‐1 and 2,7‐dichlorofluorescein diacetate (DCF‐DA) by flow cytometry respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Transition metal complexes remain a significant resource to produce chemical diversity in the search for new diagnostic and therapeutic agents, for a relatively readily subtle or dramatic change of the characteristics of the complex by alter‐related ligands. Therefore, biological applications of transition metal complexes have been greatly explored, especially in the anticancer drug development Cisplatin (CDDP), oxaliplatin (OXA), and carboplatin represent the most active and useful clinical transition metal anticancer agents, approximately nearly 50 % of all anticancer therapies globally. These drugs are especially effective in treating lung and ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Dual Functional Half‐Sandwich Ru(II) Complexes: Lysosome‐Targeting Probes and Anticancer Agents

Liu

Kong

et al. 2019

Eur J Inorg Chem

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It is known that the proposed biologically active form of ruthenium is its oxidation state II other than oxidation state III, and ruthenium complexes offer the potential of a novel mechanism of action, reduced toxicity. Herein, three half‐sandwich RuII complexes [(η6‐p‐cym)Ru(N^N)Cl]PF6 were designed and synthesized. Lysosomes are involved in various aspects of cancer cell immortalization and cell death. Thus, lysosomes are attractive pharmacological targets for selective killing of cancer cells. We demonstrated that Ru2 can accumulate in lysosomes. In addition, A549 cell viability remained at 87.81 % after exposure to Ru2 for 24 h at the working concentration. Meanwhile, Ru2 exhibited relatively high photostability and suitability for long‐term tracking. At increased concentration after 24 h of exposure to the complex toward A549 cell line, Ru2 induced a high apoptotic rate, cell cycle arrest, mitochondrial membrane potential loss, and reactive oxygen species overload. Ru2 integrated the anticancer properties and imaging capabilities and is expected to be developed as a dual functional theranostic agent.

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Apoferritin‐Cu(II) Nanoparticles Induce Oncosis in Multidrug‐Resistant Colon Cancer Cells

Xiong,

Lin,

Kou

et al. 2023

Adv Healthcare Materials

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Multidrug resistance (MDR) limits the application of clinical chemotherapeutic drugs. There is an urgent need to develop non‐apoptosis‐inducing agents that circumvent drug resistance. Herein, four therapeutic copper complexes encapsulated in natural nanocarrier apoferritin (AFt‐Cu1‐4) are reported. Although they are isomers, they exhibit significantly different organelle distributions and cell death mechanisms. AFt‐Cu1 and AFt‐Cu3 accumulate in the cytoplasm and induce autophagy, whereas AFt‐Cu2 and AFt‐Cu4 can quickly enter the nucleus and trigger oncosis. Excitedly, AFt‐Cu2 and AFt‐Cu4 show a strong tumor growth inhibition effect in mice models bearing multidrug‐resistant colon xenograft via intravenous injection. To the best of the authors’ knowledge, this is the first example of metal‐based nucleus‐targeted oncosis inducers overcoming multidrug resistance in vivo.

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Oncosis-inducing cyclometalated iridium(iii) complexes

Abstract: A series of mitochondria-targeting cyclometalated iridium(iii) complexes activated the oncosis-specific protein porimin and calpain 1, and exhibited good inhibitory activities on a wide range of cancer types including drug-resistant cancers.

Cited by 115 publications

References 80 publications

The Cell Death Phenotype of MGC-803 Cells Inducing with “Dextran-Magnetic Layered Double Hydroxide-Fluorouracil” Drug Delivery System and Fluorouracil

The Cell Death Phenotype of MGC-803 Cells Inducing with “Dextran-Magnetic Layered Double Hydroxide-Fluorouracil” Drug Delivery System and Fluorouracil

Dual Functional Half‐Sandwich Ru(II) Complexes: Lysosome‐Targeting Probes and Anticancer Agents

Apoferritin‐Cu(II) Nanoparticles Induce Oncosis in Multidrug‐Resistant Colon Cancer Cells

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